The Principal Investigator has proposed a novel overall hypothesis and approach to understanding the pathophysiology of adult periodontitis (AP), one of the most common of diseases that afflict the US population. While mortality of the dentition is the most familiar outcome of AP, its links with other more severe diseases, including coronary artery disease, respiratory diseases and pre-term labor cannot be ignored. These investigators have called attention to the many intriguing parallels between AP and contact hypersensitivity (CHS). CHS is among the most common of dermatoses that afflicts mankind and one of the most intensively studied of in vivo immune responses. Both AP and CHS target the host integument (gingiva or skin) and appear to involve the activation and sensitization of similar subsets of antigen capture and presenting cells, the dendritic cells. Dendritic cells have been termed "Nature's adjuvant," being more efficient at antigen-presentation than macrophages or B cells and the only antigen-presenting cells (APCs) than can stimulate naive T cells to proliferate. This immunostimulatory capacity can also have detrimental effects for the host, as typified by contact hypersensitivity (CHS) responses. Both AP and CHS involve a predominantly destructive T cell response mediated by both regulatory and effector T cells. These investigators have shown that Porphyromonas gingivalis is a unique pathogen in this regard, able to infect, sensitize, and activate dendritic cells in vitro and likely, in situ. Many questions about the role of P. gingivalis-sensitized dendritic cells in AP, however, remain unanswered. The present proposal will definitively establish, using in situ, ex vivo and in vitro approaches, the role of dendritic cells in adult periodontitis, particularly that induced by P. gingivalis. Moreover, these studies will characterize the interactions of P. gingivalis with dendritic cells and will further our knowledge of the pathophysiology of AP as it relates to CHS. Future studies, outside the purview of this proposal, will involve understanding the T cell response to P. gingivalis-activated dendritic cells.